SEROTONIN METABOLISM IN MYOCLONUS AND EPILEPSY

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Therapeutic trials of L-5-hydroxytryptophan (L-5HTP), the precursor of serotonin, in combination with the peripheral decarboxylase inhibitors (carbidopa, benserazide) and the serotonin uptake blocker fluoxetine will be evaluated in patients with diseases associated with myoclonic muscle movements (eg. intention myoclonus, progressive myoclonus epilepsy, essential myoclonus, palatal myoclonus, etc.). The pharmacokinetics of acute and chronic therapy with L-5HTP will be evaluated by measurement of plasma concentrations of L-5HTP, 5-hydroxyindoleacetic acid and platelet serotonin and CSF L-5HTP. The optimum dosage schedule, safety, clinical and biochemical effects of these drugs will be determined. We have found that p,p'-DDT produces a stimulus-sensitive myoclonus in rodents that is neurologically similar to human intention myoclonus. DDT myoclonus is improved by serotonin agonists and clonazepam and aggravated by serotonin antagonists as observed in the human disorder. Further studies are planned to determine the pathophysiology, biochemistry and neuronal circuits involved in the production of DDT myoclonus.